PATHOLOGY
The pathology of lead poisoning has formed the subject of scientific
inquiry from the time that the association of certain pathological
symptoms was definitely correlated with poisoning by means of the metal
or its salts.
Acute poisoning, due to accidental swallowing of large doses of lead
salts or to use of lead salts criminally, generally produces a train of
symptoms different from those met with in chronic industrial poisoning.
But it is difficult to understand why so many writers upon the subject
of lead poisoning should have attempted to draw a hard-and-fast line
between the pathological symptoms in acute and chronic poisoning.
This is especially the case when the after-history of cases of acute
poisoning is traced, for in a large number of instances a case of
acute poisoning drifts on into a subacute, and finally a chronic,
stage. All the symptoms of paralysis, encephalopathy, and even kidney
degeneration, have been described in persons who were first of all the
subjects of acute poisoning.
The direct effect of a lead salt, such as the acetate, upon the mucous
membrane of the stomach, is a caustic one, and the attention of
observers seems to have been focussed on what is really a secondary
effect of the lead salt, and not one intrinsically associated with
actual poisoning by the metal itself.
A good deal of experimental work has also been performed in one way
or another--mainly by feeding with, or inoculation of, considerable
quantities of soluble lead salts--but, with one or two notable
exceptions, such experiments have not carried the knowledge of the
true pathology of lead poisoning very much farther. The statement is
not uncommonly made that no definite correlation exists between the
symptoms observed in animals and those observed in man, the reason
being that the massive doses given to animals cannot be similar to,
nor can they produce results comparable with, the slow intoxication
taking place in man; although the after-history of the majority of
cases of acute poisoning shows that the symptoms suffered are generally
identical with the severer symptoms seen in cases of chronic poisoning
of industrial origin. One of the chief reasons explaining this
remarkable point of view arises from the fact that the tissues which
come into the hands of the pathologist for post-mortem and histological
examination are as a rule derived from cases of chronic poisoning,
cases in which the acute symptoms have drifted into the subacute or
chronic stage, when any minute changes existing in the initial stages
of the poisoning have long since disappeared, or their significance has
been so far obscured by secondary changes that the primary lesions are
lost sight of.
A critical examination of the very large amount of literature published
on lead poisoning negatives the idea that acute and chronic poisoning
differ fundamentally in their pathology, and observers are found
describing identical pathological lesions resulting from acute or
chronic industrial poisoning. It is impossible to review the whole of
the existing literature. Kobert[1], in summing up the general effect of
lead upon the animal body, makes the following general statement: “Lead
affects especially the striped and unstriped muscles, the epithelium of
the excretory glands, the neuroglia of the central nervous system, and
is essentially a protoplasmic poison.”
We base our knowledge on definite experiments, so arranged that the
method of exposure was in every way similar to that in lead industries.
The only point of difference that can be urged against them is one
of degree; but as the train of symptoms produced was in every way
comparable with those suffered by man, this objection cannot be
sustained. The fact that the symptoms develop in a shorter time than
they do in industrial processes is merely a function of the intensity
of the poisoning.
An attempt will be made first to summarize the literature on the
pathology of lead poisoning, and, as such literature covers an immense
amount of ground, to group the pathological findings of various
observers, as far as possible, under four main headings--namely:
Gastro-intestinal system.
Nervous system.
Excretory system.
Circulatory system.
=Gastro-Intestinal.=--As the chief early symptom of all types of
chronic poisoning is abdominal colic, early investigators turned their
attention to the pathology in this region, and ascribed the colic to
various causes.
Oliver[2] noted that, in animals poisoned with lead, the intestine was
found to be irregularly contracted, and ascribed the pain in abdominal
colic to the irregular contraction of the intestines themselves,
supposing that the effect of lead was on the muscular tissues. He also
noted the presence in the intestine, both large and small, of staining
due to lead, and the considerable amount of lead to be found in the
large intestine. We have only met with staining by lead in the large
intestine.
Dixon Mann[3] pointed out that the fæces contain two-thirds of the
amount of lead taken by the mouth in experimental cases, and considered
that the lead was re-excreted into the intestine; and a number of other
observers hold this view. Recent work confirms the supposition, and
there is no doubt that lead is eliminated in this way.
Stockvis[4] has occasionally seen small ulcers or abrasions in the
small intestine; these he thinks may be due to small hæmorrhages.
Ménétrier[5], quoted by Meillère, describes a form of glandular
atrophy of the stomach which is met with in chronic lead poisoning. He
states that the alcoholic gastritis generally present in persons the
subject of saturnine gastritis renders the differentiation exceedingly
difficult. This observer is also in complete agreement with many others
who associate much of the chronic lead poisoning to association with
alcoholic intemperance. The particular type of gastric degeneration
Ménétrier regards as due to the effect of lead is “une sclérose
regulière, inter-tubulaire, se recontrant d’une manière diffuse et
générale dans le muqueuse gastrique.”
He further considers that this gastric sclerosis occurs earlier than
the disease of the kidneys.
Kussmaul and Meyer[6] describe a chronic intestinal catarrh with
chronic degenerative changes in the intestinal mucosa very similar to
the changes described by Ménétrier.
Tanquerel[7] inclined to the view that the colic was not associated
with spasm of the intestines, and states that no clinical evidence
could be found of intestinal spasm by rectal examination during a spasm
of colic. But, as Bernard[8] points out, intestinal spasm may occur
with “ballonment” of the rectum.
Another cause of colic is suggested by Bokai[9]--namely,
hypersensibility of the intestinal nerves--and he cites as evidence
the diminution in pain produced by the administration of morphine; and
it is not improbable that some hypersensibility of the nervous system
of the intestine goes hand in hand with the vaso-constriction that has
been shown to exist, while, in addition, many observers have found
degenerative and even subacute inflammatory changes in the sympathetic
nervous system of the abdomen, mainly in the splanchnic area and the
solar ganglion. The action of vaso-dilator drugs on the pain of colic
demonstrates the close association of vaso-motor changes with the acute
paroxysmal pain.
Riegels[10] investigated the cause of colic in 200 cases. He found
that in every instance there was reason to suppose that toxic
vaso-constriction of the vessels in the splanchnic area, due to
irritation in the vaso-constrictor nerves, was brought about by the
action of lead.
Definite gastritis has also been described in some way simulating that
caused by arsenic, with thickening in the submucosa of the stomach and
intestine. Associated with this enteritis is endarteritis, atrophy of
the glands, and Lieberkühn’s follicles. In the colon as well as the
ileum was a well-marked enteritis involving the muscular lesions of the
gut.
Various other authors describe degenerative processes with cirrhotic
changes in the gastro-intestinal tract. Amongst these, Galvini[11]
describes, in a case of death from very chronic lead poisoning, extreme
cachexia, perihepatitis, perisplenitis, atrophy of the stomach, liver,
and spleen, and chronic sclerosing peritonitis (saturnine peritonitis).
Associated with general changes in the abdominal cavity, marked
inflammation and sclerosis was found in the solar plexus. There is
said to be a very considerable correspondence between the condition of
the peritoneal cavity and its contents in lead poisoning and barium
poisoning. In some of the animals referred to in the description of the
experiments, marked inflammatory conditions of the small intestines and
colon were found, and in not a few instances definite ulceration and
signs of recent hæmorrhages were found scattered along the intestinal
tract. No sclerosis was found, however, in the peritoneal cavity,
though a common symptom of all the animals, whether poisoned by
inhalation, inoculation, or feeding, was the absence of practically all
fat from the peritoneal cavity, the omentum being represented by an
exceedingly thin membrane without any traces of fat whatever.
=Nervous System.=--Perhaps the oldest classical symptom of lead
poisoning is the potter’s palsy or wrist-drop due to interference
with the nerve-supply of the extensor muscles of the hand, leading to
inability to extend the wrist or the fingers on the arm, wasting of
the affected extensor muscles, and finally a claw-shaped hand due to
contractions produced by the pull of the unopposed flexor groups.
The origin of this extensor paralysis has been the subject of much
controversy. One party regards the lesion as of central origin,
affecting the upper motor neurons or their connections in the spinal
cord; the other takes the view that paralysis is mainly of a peripheral
type. Tanquerel[12], whose classical work on lead poisoning still
contains one of the best descriptions of the disease from the clinical
standpoint, describes an associated affection of the peripheral sensory
nerves resulting in definite anæsthesia and hyperæsthesia, and there is
no doubt that sensory nerve affection, although not very common in lead
poisoning, does occur occasionally, and is due to peripheral affection
of the nerves. Occasionally generalized peripheral neuritis is to be
met with, but even this is much less common than in alcoholism or other
toxic forms of peripheral neuritis.
In the opinion of most of the observers who regard the neuritis as of
peripheral origin, the ultimate interference with the motor nerves is
due to an ascending neuritis of the peripheral nerves affecting the
spinal ganglia, and Pal and Mannaberg[13] have described polyneuritis;
whilst Westphal[14], Dejerine[15], Eichhorst[16], Ramond[17], and
others, support particularly the primary lesion of the peripheral
nerves as the cause of the disease. Marie and Babinski[18] in 1894
evolved the central theory, and supported it by reference to the
apparent bilateral occurrence of the paresis and the analogy with many
examples of polymyelitis. Vulpian and Steiglitz[19], examining cords
of animals poisoned by lead, described vacuolation of the cells in the
anterior cornua of the cord.
The original suggestion of the spinal origin of the disease was
enunciated by Erb[20], who, without particular reference to either the
electrical or histological changes to be found in lead poisoning, based
his theory on the similarity of the lesions to polymyelitis. A few
cords of persons who have died of lead poisoning do show slight changes
in the anterior cornua.
One other theory of the nerve affections in plumbism is that
advanced first of all by Hitzig[21], and later by Boerwinkel[22] and
Eichhorst[23], who regard the initial disease as one related to the
circulation, and not necessarily to the nerve lesions themselves.
Potain[24], basing his observations on the anatomical distribution
of the blood vessels, points out that the flexor muscles, excluding
the supinator longus, are drained by the median cephalic vein, whilst
the extensors are drained by the interosseous--a peculiarity of
considerable importance, as the supinator longus escapes paralysis in
the majority of cases of wrist-drop.
The presence of paralysis in the muscles and the association of nerve
lesions to muscular paralysis led investigators to examine the nervous
system, and probably more attention has been paid to the pathology of
poisoning in this direction than in any other. Many records of isolated
cases are to be found in the literature of the subject, and the
examination of the spinal cord has been carried out in many instances;
several have been cases of generalized paralysis or dementia, with
involvement of the trunk muscles as well as those of the extremities in
the paresis.
Many observers who have made histological examinations in such
cases have found nuclear changes in the anterior columns of the
cord suggesting polymyelitis. A small number only of the total
cases of paresis, however, come under this heading. Vulpian[25],
Oppenheimer[26], Oeller[27], and others, described degenerative and
proliferative changes in the grey matter of the cord. Steiglitz[28]
by animal experiments produced inflammatory processes in the anterior
grey substance, vacuolations in the ganglion cells, and degeneration
in the anterior root ganglia. In the paralyzed muscles the changes
of degeneration are found: the muscle nuclei become spindle-shaped,
the interstitial tissue undergoes degeneration, the muscle becomes
atrophied, takes the stain badly, shows irregular striation, and the
muscle bundles become ill-defined and fused.
Scarcely any two observers are agreed as to the exact nerve lesions
which are to be found, and so at variance are the various theories
based upon the pathological findings that it is by no means uncommon to
find two sets of observers quoting the same electrical reactions and
histological appearances as proving in the one case peripheral, and
in the other the central, origin of the paralysis. On the other hand,
in the quite early observations of Hitzig[29] particular attention was
called to the bloodvessels and their possible association with the
disease. Moreover, as has been already cited, ancient physicians were
in the habit of making use of lead as a styptic and hæmostatic because
of its peculiar action on the blood.
Probably as a result of improved histological methods of examining
the nervous tissue, renewed attention was given to the nerve fibres
and nerve cells, with the result that, in the very large number of
observations recorded, many different nerve lesions are described as
the sequelæ of lead intoxication.
On the other hand, Hitzig’s observations on the associated inflammation
of the bloodvessels has received confirmation by several independent
workers. Westphal[30] cites a case of chronic lead poisoning resulting
in death from encephalopathy, and describes degeneration and œdema of
the brain following a process of chronic inflammation in the smallest
and minute bloodvessels, and also associated with degeneration of
the ganglion cells in the vicinity. Chvostek[31] also publishes a
similar case where cerebral degeneration and some œdema had occurred.
Kolisko[32], in examining the brain of a girl who had died of
encephalopathy, found chronic œdema of the brain and spinal cord,
the condition closely resembling that described by Hitzig as chronic
cerebral hypertrophy.
Quensel[33], in a man who had died of encephalopathy, found
leptomeningitis, atrophy of the cortex with degeneration of the
parenchymatous elements of the cells and nerve fibres, degenerative
changes in the vessels, nuclear destruction and pigmentation of the
cells, and œdema. Nissl[34] described granules, which bear his name,
present in the ganglion cells in the cortex, with parenchymatous
degeneration. These cases were not associated with paralysis, nor
is encephalopathy by any means always complicated with paralysis of
muscles.
Berchthold[35] describes a case of typical spastic paraplegia due to
lead, and states that the cortical neurons were but little damaged, the
weight of the poison having fallen upon the peripheral segments.
Sorgo[36] describes a case of progressive spinal muscular atrophy
traced to lead, in which degeneration of the spinal cord was a marked
feature.
Steiglitz[37], in describing the inflammatory processes produced
in animals poisoned by lead, makes special mention of a distinct
minute inflammatory change in the grey matter of the brain, with
vacuolation occurring in the ganglion cells in the anterior horns of
the spinal cord. Prévost and Binet[38], on the other hand, describe an
inflammation of the peripheral nerves occurring after administration of
lead to rabbits for one month. They produced what they describe as “a
lead polyneuritis,” with primary affection of the motor nerves. With
the brain, as with other parts of the body, various writers describe
widely differing changes. Experimentally, when the doses have been
massive and the animals rapidly poisoned, very little has been found,
and some regard this as evidence against the central origin of lead
paresis. On the other hand, in cases of chronic poisoning (mainly
chronic industrial poisoning), where an opportunity of post-mortem
examination has been afforded, marked atrophic changes have been
discovered both in the brain and spinal cord, in the motor nerves
supplying the affected muscles, and throughout the nervous system
generally, so much so that anterior polymyelitis of old origin is
described, vacuolation and degeneration of the ganglion cells, and
various other pathological changes associated with nerve degeneration.
On reviewing the literature, it becomes practically certain that in
the old and advanced cases of poisoning lesions are invariably found
in the central nervous system, while in the less advanced cases the
most marked change has been found in the peripheral nerves. In only a
very few instances have any observers noted the fact of hæmorrhages
occurring in the nervous tissues, and one of the most important
observations on this point is the careful description by Mott[39], of a
fatal case of lead poisoning in an asylum, in which distinct yielding
of the vessel walls with minute hæmorrhages was present in the cerebral
cortex. This case is quoted in full on p. 71.
In the record of the experiments by one of us (K. W. G.) on p. 95 are
described the hæmorrhages occurring in the anterior crural nerves of
cats poisoned by lead. These animals showed most distinct loss of power
in their hind-limbs, as was evidenced by their inability to jump,
and other symptoms homologous to wrist-drop in man. In these animals
no nerve degeneration or alteration in the spinal cord was found
sufficiently gross to account for the paralysis, whereas the amount of
pressure produced by the yielding of the vessel walls on the nerve
bundles and the associated exudation was evidently sufficient to cause
compression, and thereby loss of function in the nerve in question.
Now, the pathological changes described by numerous observers, such as
parenchymatous and interstitial changes in the brain, destruction of
the anterior grey matter, and, finally, the degenerative changes in
the muscle groups, the macroscopical and microscopical atrophy of the
muscle bundles with the fibrillation and other changes, are none of
them opposed to the view that hæmorrhage and exudation are the earliest
and initial change; in fact, in experimental animals minute hæmorrhages
could always be traced in the earliest stages of poisoning, frequently
before definite symptoms appeared.
Confirmation of this theory is seen in the work of Glibert[40], and the
drawings he gives showing fibrous changes in the lungs, hyperplasia,
congestion, and emphysema, cirrhotic conditions of the liver, and, as
he describes it, blood-stasis caused by elongation and dilatation of
the capillaries, are all of them highly confirmatory of the hæmorrhage
theory. Further confirmation is also afforded by the observations on
the action of lead salts upon the blood itself. From the earliest days
lead has been used as a styptic, and its empirical use has been shown
by later observation to be due to its power of readily coagulating
albumin and peptone. Further, in chronic lead poisoning there is a
marked increase in the coagulation time of the blood. Glibert, in
the work already referred to, points out the increased ductility of
the red blood-cells in lead poisoning. Quite apart from this, there
is no doubt that definite alterations in the red blood-cells occur;
a species of icterus is common in lead poisoning, the anæmia of lead
poisoning is of a destructive type, increased urobilin may occur
in the urine, and in some instances hæmatoporphyrin is present in
considerable quantities. The bone-marrow in cases of lead poisoning
undergoes distinct inflammatory change, and may possibly be the cause
of some of the curious aching arthralgias often noted as a clinical
symptom. All the pathological evidence that can be adduced points
unmistakably to the blood as suffering the initial stress in lead
poisoning, and it is therefore by no means surprising that the blood
vessels should be the next in order to undergo degenerative changes.
It is probably this degenerative change, particularly associated with
the increased coagulability, alteration in viscosity, the destruction
of the blood-cells themselves, and the permeation of the vessel
walls by definite, if exceedingly minute, quantities of lead salts,
that determines the yielding of the smaller and generally the weaker
bloodvessels. In the histological examination of the experimental
animals there was considerable evidence that the venules, rather than
the arterioles, are the first to yield.
The following case of chronic lead encephalitis, with the examination
of the nervous system described by Mott[41], is a case that has a large
bearing on the general pathology of lead poisoning, and has the merit
of being so carefully described that we cite it at length, as bringing
out some of the special features connected with the pathology of lead
poisoning.
The patient was a coach-painter, aged forty-four. Family history of
no particular interest. Had been a painter since a boy. No specific
history. Treated for enlargement of liver at one time. Married. No
children. His wife a widow; four children before married to him.
Before the attack of encephalitis, which ultimately resulted in
his death, he suffered from colic and obstinate constipation. The
commencement of the final attack of lead infection was associated
with an epileptiform fit, from which he recovered and resumed his
work, but from this time onwards he suffered from progressive
weakness and progressive inability to perform his ordinary work.
Constant indulgence in alcohol did not pull him together as before;
and although previously he had been able to indulge in large
quantities of alcohol, a very little now affected him adversely.
The first epileptiform attack was in July, and in November he
commenced to have delusions, was restless, suspicious.
On admission to the asylum he showed marked cachexia. Weight, 8 stone
7 pounds; height, 5 feet 9 inches. There was present well-marked oral
sepsis and blue line.
_Mental Condition._--Restlessness; disorientation; remitting
delirious state; periods of shouting coincident with colic, worse at
night; auditory hallucinations.
_Physical Condition._--Bilateral wrist-drop; extensor paralysis of
the fingers; hand-grip and gait impaired; reaction of degeneration
of paralyzed muscles; coarse tremors; fibrillary twitching; staccato
articulation.
_Sensory._--No definite change.
_Reflexes._--Pupils normal. Sluggish reaction to light and
accommodation.
_Organic._--Deglutition difficult. Micturition and defæcation not
under control.
_Vaso-motor._--Tâche cérébrale marked.
Eye neuro-retinitis. Unequal amaurosis.
_Heart._--Increased action, variable; alteration during exacerbations
of colic. Second sound in aortic area accentuated. High pressure,
variable. Majority of arteries thickened.
He suffered gradual mental change; the whole of the mental symptoms
increased in severity until the patient looked like the final stages
of a case of general paralysis. He died on December 1. Colic was
present at intervals during the whole time.
Post-mortem made the next day. Septic bronchitis. Hæmorrhage at the
base of epiglottis and left vocal cord.
_Lungs._--Septic broncho-pneumonia.
_Pericardium._--Small amount of fluid.
_Heart._--Striated, bluish. Weight 11¹⁄₄ ounces.
_Ventricles._--Slight hypertrophy of left ventricle.
_Valves._--Competent.
_Aorta._--Atheroma near its bifurcation.
_Arteries._--All more or less thickened.
_Peritoneum._--Retroperitoneal hæmorrhage in region outside pancreas.
Mesenteric glands enlarged, indurated, bluish on section.
_Stomach._--Normal.
_Intestines._--Vessels congested. Large bowel constricted at
irregular intervals.
_Cæcum._--Mucosa slate-coloured.
_Colon._--Dark-greenish mass.
_Liver._--Blue on section; pale yellow areas; soft in consistency.
Weight, 47³⁄₄ ounces.
_Spleen._--Normal.
_Kidneys._--No fat. Cirrhotic, adherent, atrophic cortex, granular.
_Muscles._--Generally dark in colour; wasted.
A very complete histological examination was made of the brain and
spinal cord, and throughout the particular changes noticed were
proliferation of the glia, hyaline thickening of the walls of the
vessels, both arteries and veins, and presence of congestion; and
here and there rupture of the smallest vessels, causing miliary
microscopic hæmorrhages into the perivascular sheaths and the
substance of the brain. There was no infiltration with lymphocytes
and plasma cells, as is found in general paralysis. The neuroglia
showed a formative hyperplasia resulting from chronic irritation.
In the cortex there was neuroglia proliferation in the polymorpho
layer and the molecular layer. Changes were seen in the Betz cells,
particularly in the Nissl substance, with perinuclear chromatolysis,
such as is generally found in chronic peripheral neuritis, whether
due to lead, alcohol, or other toxic causes.
There was no coarse atrophy or degeneration of the fibres of the
cortex. Neither the cerebellum nor the spinal cord at any of the
levels examined showed fibre atrophy or degeneration, except possibly
a slight diffuse sclerosis in the crossed pyramidal tracts of the
lumbar region.
Microscopical examination was made of the heart, spleen, kidney,
liver, lung, and suprarenal gland. There was a general condition
of angiosclerosis; in the liver a fibrotic overgrowth around the
vessels; in the kidneys well-marked interstitial fibrosis.
A chemical examination of the brain was also conducted by the copper
potassium nitrite method, but no lead was found.
=Excretory System.=--A large number of observers have shown that great
stress is thrown on the kidney in the excretion of lead. Discussion
has taken place as to whether the effect is a primary interstitial
or a parenchymatous nephritis. Most observers are agreed that the
histological changes found in the kidneys of lead workers have very
little by which they may be differentiated from the effects of alcohol.
Although the kidney suffers directly from the effect of circulating
lead, the amount of lead excreted by the kidney in chronic cases is
usually small, variable in quantity, and very rarely exceeds more than
5 milligrammes in the twenty-four hours.
The chemical estimations of the quantity of lead found in the kidney of
persons who have died of lead poisoning given by different observers,
vary exceedingly. Even in cases of definite lead poisoning, where there
can be no reasonable doubt as to the diagnosis, many cases are on
record where no lead at all has been discovered in the kidney.
It is not acute nephritis which is seen in lead poisoning, but the
chronic cirrhotic variety. This probably takes a very long time to
develop; indeed, animals kept under the influence of lead for two years
show very little kidney destruction. It is quite possible that in the
kidney disease met with in lead-workers the combined effect of alcohol
with lead is really the causative factor. There is not sufficient
statistical evidence to make a definite statement on this point, and it
would only be possible by comparing the records of the autopsies of a
number of persons working in lead who do not die from lead poisoning,
and who were non-alcoholic, with a similar number of persons who, in
addition to their lead absorption, were alcoholic subjects.
It is unusual to find blood in the urine, and the condition of the
kidney does not suggest that it would be present.
Gull and Sutton[42] have described arterio-capillary fibrosis in which
the intima of the larger vessels became greatly hypertrophied, and
many of the smaller vessels are practically destroyed by obliterative
arteritis. The production of arterio-sclerosis, with attendant
thickening of the vessel walls and with the various symptoms commonly
associated with arterio-sclerosis, were regarded as secondary symptoms
of lead poisoning. The action of lead on the vessel walls themselves
thus independently proved by a large number of observers working at
different aspects of the problem suggests the pathological change
in the vessels as the common element in the cause of these diverse
symptoms of lead poisoning--colic, paralysis, mania. Generally
speaking, however, the attention of most has been rather focussed on
the kidney and the degenerative changes occurring in that organ due to
the irritative action of lead in the process of excretion than on the
vessels themselves.
Lead in the urine is by no means so common nor so definite a symptom
of lead poisoning as might be supposed, considering the extreme manner
in which the kidneys suffer in old-standing cases. Of particular
importance in this respect is the case referred to by Zinn[43], where a
woman aged thirty-three received 20 grammes of lead acetate in error.
After the first acute symptoms had passed off, the case drifted on to
one of chronic poisoning, with the usual symptoms of colic, anæmia,
and cachexia. During the whole period of the disease, both acute and
chronic stages, examinations of the urine for lead were made, using
the method of Fresenius Babo[44]; yet lead was only detected in the
urine during the early stages, and directly the acute symptoms had
passed off no further lead could be detected. This point is of some
importance, particularly when taken together with the experiments
quoted by Blum[45], who, injecting animals with lead iodide, was unable
to recover lead from the urine. The iodide only passed through the
kidney, the lead being retained in the body.
Jaksch[46] states very definitely that lead is not found in the urine
in chronic cases, but only in the acute cases, and then quite early.
With regard to the kidney two views are held--the one regarding the
disease of the kidney as primarily affecting the bloodvessels, and the
other as an initial parenchymatous change causing secondary obstruction
and alteration in the vessels themselves. There is therefore much
evidence to show that, whether the bloodvessels be primarily or
secondarily affected, almost all observers are in accord in the opinion
that at one time or another, either sooner or later, the bloodvessels
become affected through the action of lead.
Kobert[47] points out that in no case was distinct cirrhosis of the
kidney produced in experimental lead poisoning in animals; inflammation
certainly was to be seen, either interstitial or parenchymatous, but
apparently the poisoning had not progressed a sufficient length of
time for definite cirrhosis to be produced. On the other hand, kidney
changes have been found of various types, all of which may be the
precursors of the ultimate cirrhotic and fibroid change occurring in
the kidneys seen in chronic poisoning by lead as well as in chronic
alcoholism. Particular stress must be laid on the fact that cirrhotic
kidneys are so frequently the direct result of long-continued alcoholic
excess, and, from what has been demonstrated in the experimental
researches on predisposition to lead caused by alcohol, the condition
of cirrhosis of the kidney in a lead-worker is by no means indicative
of lead poisoning, as it may be an old alcoholic effect long antedating
that due to lead.
Oliver[48], Charcot[49], Gombault[50], Hoffer[51], and others, found a
certain amount of parenchymatous degeneration. Von Leyden[52], however,
was able to produce a granular condition of the kidney with glomeruli
shrunken and an arterio-capillary fibrosis. Gayler[53], on the other
hand, thinks that the arteritis of the smallest arteries is the
preliminary effect upon the kidney, whereas more recently Glibert[54]
published plates of the kidney showing definite sclerosis as well as
interstitial nephritis.
Cornil[55] and Brault[56] think the vessels are affected only
secondarily, and that parenchymatous changes are the primary lesion.
Hoffer[57], by feeding guinea-pigs with lead, produced very definite
obliterative arteritis. Klemperer[58] claims to have produced
inflammation and definite necrosis of portions of the kidney substance.
The whole of the kidney is not necessarily affected. Only portions of
it may show changes, while Kleinenberger[59] notes that in chronic
lead poisoning, at the time of acute exacerbation of the disease,
granular casts as well as red blood-cells are found; and, further, that
in cutting through them crystallized masses are occasionally found,
consisting of urates, and sometimes containing lead.
Gayler[60] considers that the effect on the kidney commences in the
muscular coats of the smaller vessels, in which endarteritis followed
by obliterative arteritis is set up.
Practically all observers, therefore, are in agreement that the kidney
suffers to a very considerable extent in chronic poisoning, and the
majority of observers are also in agreement that the bloodvessels
themselves are the primary seat of the change. Further, the presence
of blood in the urine is exceedingly rare in chronic lead poisoning,
despite Kleinenberger’s[61] statement to the contrary. It certainly may
occur during a very acute attack, but we have never seen this symptom.
=Circulatory System.=--Arterio-sclerosis occurring in lead-workers has
been known for some time, and the anæmia of saturnism has been known
for an even longer period. For some time no definite type of anæmia was
associated with lead cachexia, and the anæmia was generally regarded
as one arising from general malnutrition. Here and there through the
literature of the pathology of lead poisoning are to be found remarks
which suggest that the action upon the bloodvessels may be a primary
instead of a secondary effect. Obliterative arteritis is described by
Uhthoff[62], Pflueger[63], Oeller[64], and Pal[65], and in other cases
obliterative retinitis has been considered to be associated with the
action of the lead upon the vessel walls.
Heubel[66], and later Rosenstein[67], found that, in dogs
poisoned with lead, definite cerebral anæmia was produced, due to
vaso-constriction, and consider it to be due to the direct action
of lead upon the intima of the vessel walls. Associated with such
poisoning were symptoms of eclampsia and uræmia, and the latter author
considers that the uræmia is due to vaso-constriction of the kidney
vessels.
Oliver[68] and others have also pointed out the alteration in the
pulse-rate associated with exacerbations of colic, and a number of
observers have noted that certain drugs, such as atropin and amyl
nitrite, which are known vaso-dilators, have a distinctly calming
effect upon the paroxysms of pain.
One or two other observers have actually noted the presence of
hæmorrhages in the lesions; thus, in the case quoted by Mott[69]
definite yielding of the vessel walls and signs of old hæmorrhage
are described amongst other lesions in the brain. Seifert[70] also
describes the presence of hæmorrhages amongst the ganglion cells in
the anterior columns of the cord, both in the case of persons who
have died of lead poisoning and animals to which lead had been given
experimentally. In addition, Sajous[71] describes a case of paralysis
of the superior laryngeal nerve, associated with hæmorrhages, in the
region of the abductor muscles of the larynx. Mott’s case also showed
this laryngeal hæmorrhage.
More recently Elschnig[72], in his observations upon the eye, has
determined a close association between vaso-motor affections,
constrictions, and dilatations, and various eye lesions, such as
amaurosis and amblyopia, occurring in lead poisoning. Rambousek[73],
in summing up Elschnig’s work, points out how much his observations
tend to bridge over the gap between the action of lead upon the blood,
the bloodvessels, and the nerves. He points out that the eye is a
peculiarly favourable organ for watching the effect of a poison so
insidious as lead. The bloodvessels, the nerves, and the muscles, are
all open to inspection and actual observation to a degree not to be
found in any other part of the body. Elschnig[74], in a typical case of
sudden lead amaurosis associated with acute lead colic, found that very
definite motor spasm of the vessels of the eye, conjunctiva, and the
retina, were associated with the amaurosis. He argues from this that
the action of lead is probably directly upon the unstriped muscular
fibre of the vessel walls; that such an action may, and does, extend
to the vessels of the eye muscles, producing paralysis of the muscles
of accommodation, and a dilatation of the pupil, which may be observed
in a large number of persons employed in conditions subjecting them
to lead absorption. Elschnig further considers that the transitory
amaurosis which is often associated with lead poisoning may be due to
vaso-motor disturbances in the brain itself, as well as in the eye.
Still more recently, and due, no doubt, to a great extent to the work
of Elschnig, further attention has been drawn to the vascular system in
lead poisoning. Elschnig’s work has carried the question another stage
forward by showing the association of vaso-motor disturbances with eye
disease, whilst in this country Oliver[75] pointed out the effect upon
the pulse of abdominal colic.
At the beginning of the researches on this point described in the
next chapter, this clue running through the whole of the pathology
of lead poisoning was not appreciated. At the commencement of the
investigations there seemed to be no main general line of symptoms or
histological findings that could be adduced as characteristic of lead
poisoning; in fact, the initial experiments were performed, with the
object of examining the association of lung-absorbed lead compounds as
a possible cause of lead poisoning, as against the entrance of lead
by the alimentary canal; but as the experiments proceeded it became
clear that the stress of the initial intoxication was undoubtedly
falling upon the bloodvessels, and more particularly upon the minuter
bloodvessels, and less on the arterial side of the capillaries
(although the capillaries were to a large extent associated with the
process) than upon the venous radicles.
A general consideration of the pathology shows that lead causes
changes in the nervous system affecting both upper and lower segments,
degeneration of the ganglion cells in the cord and in the brain,
interstitial inflammation of the neuroglia, cortical degeneration,
distinct neuritis, both axial and peri-axial, of the peripheral nerves,
and also signs of change in the sympathetic nervous system in chronic
lead poisoning. Later work has, however, all tended to point out that
the chief and first effect of lead is upon the blood.
Moritz[76] first pointed out the presence of basophile granules in the
red blood-cells. The work was followed up by Emden[77], Gravitz[78],
Zinn[79], Otto[80], Silbert[81], and by Escherich[82]. All these
authors found basophilic erythrocytes in the blood associated
with blood-destruction, and Escherich in addition describes early
changes taking place in the intima of the bloodvessels associated
with vaso-constriction. The Italian author Mattirolo[83], as well as
Marchet[84] and Jores[85], came to a similar conclusion. Glibert of
Brussels[86], carrying the observations somewhat farther, and although
working with guinea-pigs, which normally show basophilic staining
in their blood-cells, was able to demonstrate one further point of
considerable value--namely, the increase in the viscosity of the blood,
with blood-corpuscles of greater toughness, elasticity, and power to
resist destruction when making films, than in normal blood.
There is thus very striking continuity in the observations of all
the various observers, despite the fact that at first sight their
descriptions may appear discordant. There seems no doubt that
practically all authors who have given attention to the subject are
agreed that the circulatory system, and primarily the blood circulating
in the vessels, is affected by lead, and, further, that the vessels
themselves undergo degeneration of various types, many of the cases
examined showing complete obliterative arteritis as the result of
long-standing irritation. Others describe no obliterative changes of
this type in the vessels, because attention was given mainly to the
nervous system, where the cells were found degenerated and showing
chromatolysis. But, on the other hand, careful observers, such as Mott,
have noted the presence, in passing, of these apparent yieldings of
the vessels here and there in the region of the degenerated nervous
tissue. Again, even the histological action of a drug such as amyl
nitrite points to involvement of the vaso-motor system. Perhaps
this curious association through all the described pathology and
bloodvessel infection would not appear so clear but for the more recent
investigations described in the following chapter.
REFERENCES.
[1] KOBERT: Lehrbuch der Intoxikationen, 2te Aufl., 1906, p. 361.
[2] OLIVER, SIR T.: Lead Poisoning. 1891.
[3] DIXON MANN: Forensic Medicine and Toxicology, p. 495.
[4] STOCKVIS: International Congress of Industrial Hygiene. Brussels,
1910.
[5] MÉNÉTRIER: Meillère’s Le Saturnisme, pp. 131-136.
[6] KUSSMAUL AND MEYER: Deutsches Archiv für Klin. Med., ix., p. 283.
[7] TANQUEREL: Traité des Maladies de Plomb, ou Saturnines. Paris,
1839.
[8] BERNARD: Meillère’s Le Saturnisme, p. 155.
[9] BOKAI: Trib. Med., June 11, 1891.
[10] RIEGELS: Kobert’s Lehrbuch der Intoxikationen, p. 363.
[11] GALVINI: Rivista Clinica, fasc. iii., 1884.
[12] TANQUEREL: _Ibid._
[13] PAL AND MANNABERG: Revue Générale de Villaret, Gaz. des Hôp.,
Fév. 16 and 19, 1903.
[14] WESTPHAL: Archiv f. Phys. u. Nervenkr., 1874.
[15] DEJERINE: Mém. de la Soc. de Biologie, 1879, et Exposé de
Titres, p. 58, 1894.
[16] EICHHORST: Ueber Bleilähmung. Virchow’s Archiv, 1890, p. 217.
[17] RAMOND: Maladies du Système Nerveux, t. xi. 1895, 1896.
[18] MARIE AND BABINSKI: Meillère’s Le Saturnisme, p. 193.
[19] VULPIAN AND STEIGLITZ: Archiv für Psych., 1892, xxiv., p. 1.
[20] ERB: Berl. Klin. Woch., 1884, p. 110.
[21] HITZIG: Studien über Bleiverg. Berlin, 1868.
[22] BOERWINKEL: Virchow’s Archiv, Bd. cxx., 1890.
[23] EICHHORST: _Ibid._
[24] POTAIN: Bull. Med., 1887.
[25] VULPIAN: Maladies du Système Nerveux. 1879.
[26] OPPENHEIMER: Zur Kennt. der Exp. Bleiverg. Berlin, 1898.
[27] OELLER: Path. Anatom. der Bleilähmung. München, 1883.
[28] STEIGLITZ: Archiv für Psychiatrie, Bd. xxiv., 1892.
[29] HITZIG: _Ibid._
[30] WESTPHAL: Archiv für Psychiatrie, Bd. xix., 1888.
[31] CHVOSTEK: Neurol. Centralblatt, 1897.
[32] KOLISKO: Die Bekämpfung der Bleigefahr in der Industrie, von
Leymann, p. 21. 1908.
[33] QUENSEL: Archiv für Psychiatrie, Bd. xxxv., 1902.
[34] NISSL: Allgemeine Zeitschrift für Psychiatrie, Bd. xlv., 1892;
Bd. iv. 1897.
[35] BERCHTHOLD: Die Bekämpfung der Bleigefahr in der Industrie, von
Leymann, p. 23. 1908.
[36] SORGO: Wien. Med. Woch., 1900.
[37] STEIGLITZ: Archiv für Psychiatrie, Bd. xxiv., 1892.
[38] PRÉVOST AND BINET: Revue Médicale de la Suisse Romande, ii.,
1889.
[39] MOTT: Archives of Neurology and Psychiatry, vol. iv., p. 117.
[40] GLIBERT: Le Saturnisme Expérimental: Extrait des Rapports Ann.
de l’Insp. du Travail, 1906.
[41] MOTT: _Ibid._
[42] GULL AND SUTTON: Kobert’s Lehrbuch der Intoxikationen, 2te
Aufl., 1906, p. 370.
[43] ZINN: Berl. Med. Woch., 1899.
[44] FRESENIUS BABO: Liebig’s Annalen, vol. xlix., p. 287. 1844.
[45] BLUM: Wien. Med. Woch., No. 13, 1904.
[46] JAKSCH: Klinische Diagnostik.
[47] KOBERT: _Ibid._, p. 369, and general Literature, p. 376.
[48] OLIVER, SIR T.: Lead Poisoning. 1891.
[49] CHARCOT: Leçons sur les Maladies du Foie et des Reins. Paris,
1882.
[50] GOMBAULT: Archiv für Physiologie, 1881.
[51] HOFFER: Dissertation, Freiburg, 1883.
[52] VON LEYDEN: Zeit. für Klin. Med., 1883.
[53] GAYLER: Ziegler’s Beitr., ii., 1888.
[54] GLIBERT: _Ibid._
[55] CORNIL: Journal de l’anat. et physiol., No. 2, 1883.
[56] BRAULT: _Loc. cit._
[57] HOFFER: _Loc. cit._
[58] KLEMPERER: Kobert’s Lehrbuch der Intoxikationen, 2te Aufl.,
1906, p. 370.
[59] KLEINENBERGER: Münch. Med. Woch., No. 8, 1904.
[60] GAYLER: _Loc. cit._
[61] KLEINENBERGER: _Loc. cit._
[62] UHTHOFF: Handbuch der Aug. Lief. Leipzig, 1901.
[63] PFLUEGER: Die Bekämpfung der Bleigefahr in der Industrie, von
Leymann, p. 21. 1908.
[64] OELLER: _Ibid._
[65] PAL: Zentralbl. f. innere Med. Leipzig, 1903.
[66] HEUBEL: Path. und Symp. Chron. Bleiverg. Berlin, 1871.
[67] ROSENSTEIN: Virchow’s Archiv. 1897.
[68] OLIVER, SIR T.: Lead Poisoning. 1891.
[69] MOTT: _Ibid._
[70] SEIFERT: Berl. Klin. Woch., 1884.
[71] SAJOUS: Archiv für Laryng., iii., 1882.
[72] ELSCHNIG: Wien. Med. Woch., 1898.
[73] RAMBOUSEK: Die Bekämpfung der Bleigefahr, von Leymann, p. 15.
1908.
[74] ELSCHNIG: _Loc. cit._
[75] OLIVER, SIR T.: Lead Poisoning. 1891.
[76] MORITZ: St. Petersb. Med. Woch., 1901.
[77] EMDEN: Die Bekämpfung der Bleigefahr, von Leymann, p. 19.
[78] GRAVITZ: Deutsche Med. Woch., No. 36. 1899.
[79] ZINN: Berl. Klin. Woch., 1899.
[80] OTTO: Revue Méd., 1892.
[81] SILBERT: _Ibid._
[82] ESCHERICH: Die Bekämpfung der Bleigefahr, von Leymann, p. 18.
[83] MATTIROLO: _Ibid._, p. 19.
[84] MARCHET: _Ibid._, p. 19.
[85] JORES: Ziegler’s Beitr., Bd. xxxi., 1902.
[86] GLIBERT: _Ibid._